白细胞介素-1α在髓核源性神经根性疼痛中的作用

目的:探讨白细胞介素-1琢(IL-1琢)是否参与髓核突出所致的坐骨神经疼痛的产生。方法:将大鼠自体尾椎的髓核无压迫下放置在L4和L5神经根表面,在术后不同时间测量大鼠后足对机械刺激敏感性的变化,同时用免疫组化方法对移植髓核中的IL-1琢进行检测。结果:在无明显机械压迫的情况下,大鼠腰神经根上放置自体髓核后,术侧后足可产生明显机械刺激痛觉过敏;实验组大鼠移植髓核组织中IL-1琢免疫组织化学染色阳性。结论:髓核组织的生物学作用是引起腰腿痛的重要因素,炎性介质IL-1琢可能参与疼痛的发生。     

皮层躯体感觉诱发电位在监测腰神经根损伤中作用的研究

目的：利用大鼠髓核突出动物模型。探索皮层躯体感觉诱发电位（CSEP）的波幅和潜伏期变化是否与神经根性疼痛有关系。方法：取大鼠自体尾部的髓核无压迫下放置在L4和L5神经根上，制成髓核突出动物模型。分别在术后3d,1,2及4周观察大鼠术侧肢体机械刺激敏感性和热刺激敏感性和热刺激敏感性的变化，并引出大鼠后肢CSEP，观察术侧肢体CSEP的变化。结果：在无明显机械压迫的情况下，大鼠腰神经根上植入自体髓核可产生痛觉过敏，CSEP波幅增高。结论：髓核自身是引起腰腿痛的重要原因，CSEP波幅的增高与神经根性疼痛有一定相关性。     

硬膜外移植自体髓核对大鼠神经根功能和组织学的影响

目的：探讨无机械压迫时，腰椎间盘髓核突出引起腰腿痛的发病机制。方法：用硬膜外穿刺的方法给大鼠注射生理盐水及自体髓核混悬液，并对机械刺激缩爪阈值、马尾神经传导速度，神经根组织形态、疼痛行为进行了测定和观察。结果：大鼠硬膜外移植自体髓核能产生明显的痛觉过敏反应，马尾神经传导速度和神经根组织形态产生明显改变。结论：髓核所致的炎症反应是引起坐骨神经痛的重要原因之一。     

实验性髓核突出诱致神经根性疼痛机理的探讨

目的 探索单纯自体髓核组织放置于神经根邻近,并与神经根接触后对大鼠后爪机械刺激痛觉敏感性的影响。方法 取大鼠自体尾椎髓核组织无压迫下置于腰4和腰5神经根旁并与神经根相接触,术后不同的时间点观察大鼠双侧后爪机械刺激敏感性的变化;同时采用HE染色方法观察髓核组织和神经根的变化。结果 无明显机械压迫情况下,自体髓核组织与神经根接触后可诱导大鼠术侧后爪出现明显的机械性痛觉敏感性的升高;HE染色显示髓核组织发生了明显的炎性改变,邻近神经根出现空泡变性。结论 髓核组织自身介导的炎症反应可能参与机械性痛觉敏感性的发生。除机械因素外,突出髓核组织发生的炎症反应也可能是腰椎间盘突出所致坐骨神经痛的原因。     

硬膜外移植自体髓核对大鼠神经根功能和组织学的影响

目的:探讨无机械压迫时,腰椎间盘髓核突出引起腰腿痛的发病机制.方法:用硬膜外穿刺的方法给大鼠注射生理盐水及自体髓核混悬液,并对机械刺激缩爪阈值、马尾神经传导速度,神经根组织形态、疼痛行为进行了测定和观察.结果:大鼠硬膜外移植自体髓核能产生明显的痛觉过敏反应,马尾神经传导速度和神经根组织形态产生明显改变.结论:髓核所致的炎症反应是引起坐骨神经痛的重要原因之一.     

髓核对大鼠腰神经根非压迫性损伤的组织形态学研究

目的　观察硬膜外移植自体髓核后 ,大鼠神经根组织形态学的变化。方法　 2 8只Sprague Dawley(SD)雄性大鼠随机分成对照组和实验组 ,分别将自体肌肉混悬液和尾椎髓核混悬液注射到腰椎硬膜外腔 ,对神经根组织进行形态学观察。结果　在无机械压迫情况下 ,大鼠硬膜外移植自体髓核能使马尾神经根组织形态产生明显改变。结论　髓核所致的炎性反应是引起神经根损伤和坐骨神经痛的重要原因之一     

大鼠非压迫性髓核突出模型的建立

目的：设计一种新的非压迫性腰椎间盘髓核突出动物模型。方法：16只SD雄性大鼠随机分对照组和实验组，分别将生理盐水和大鼠自身尾椎髓核混悬液注射到腰椎硬膜外腔，对其马尾神经传导速度和神经根组织形态学进行观察。结果：无明显机械压迫情况下，大鼠硬膜外移植自体髓核能使马尾神经根传导速度和组织形态产生明显改变。结论：本动物模型简单、可靠、费用低廉，为进一步研究腰椎间盘突出症提供了一种动物模型。     

压迫及非压迫因素在实验性神经根性疼痛中的作用

目的：探讨压迫及非压迫因素在实验性椎间盘源性神经根性疼痛中的作用。方法：取大鼠白体脊椎关节突修剪后放置在L5神经根下．造成对L5神经根的直接压迫（压迫组）；取大鼠白体尾椎椎间盘组织无压迫下放置在L5神经根表面（非压迫组）：同时设立对照组。术后不同时间点测定各组大鼠后足底机械刺激疼痛阈值的变化。结果：压迫组与非压迫组大鼠后足底均产生了一个长时程机械刺激疼痛阈值的降低；与压迫组相比．非压迫组大鼠术后1天就开始出现了疼痛阈值降低（P〈0．05），明显早于压迫组大鼠，并且疼痛阈值降低更加显著：而压迫组大鼠术后1周时才出现明显的疼痛阈值降低（P〈0．05）。对照组大鼠疼痛阈值没有发生明显的改变。结论：尽管压迫和非压迫因素都参与椎间盘源性神经根性疼痛的发生．但二者作用的时间不同＋在椎间盘突出的早期阶段非压迫因素可能在疼痛中起着重要的作用：随后压迫因素可能逐渐成为致痛的主因。     

周围神经旁移植自体髓核对大鼠疼痛行为的影响

目的　探讨髓核在坐骨神经痛发病机制中的作用。方法　选择 16只SD雄性大鼠随机分为两组 ,分别将自体尾椎髓核混悬液注射到腰椎硬膜外腔或坐骨神经周围。测定其后肢机械刺激缩爪阈值。结果　在没有明显机械压迫下 ,腰椎硬膜外腔的髓核使大鼠后肢产生明显的痛觉过敏反应 ,坐骨神经旁的髓核不能使大鼠产生上述变化。结论　与髓核相关的炎症的介质是引起坐骨神经痛的原因之一 ,神经根缺乏神经外膜保护是引起疼痛的解剖学基础。     

实验性坐骨神经痛中辣椒素敏感初级传入纤维的作用

目的 通过局部破坏坐骨神经中辣椒素敏感传人纤维(CSPA),确定CSPA在自体椎间盘直接压迫L5神经根所诱导的机械刺激痛觉过敏的作用.方法 取大鼠自体尾部椎间盘组织放置在L5神经根下,造成对L5神经根的直接压迫,建立椎间盘突出致坐骨神经疼痛动物模型.同时暴露大鼠左侧坐骨神经,给予辣椒素溶液或溶媒处理.术前及术后不同的时间点测量大鼠双侧后足底机械刺激疼痛阈值的变化.在3周当机械刺激疼痛阈值降到最低时,利用免疫组织化学染色方法,测定脊髓后角中c-fos蛋白空间表达变化.结果 用辣椒素处理坐骨神经,完全阻止了椎间盘压迫神经根所诱致的机械刺激疼痛阈值的降低.椎间盘直接压迫L5神经根能够诱导后角中c-fos蛋白表达,而辣椒素处理坐骨神经能够抑制后角中c-fos蛋白的表达.结论 主要终止于脊髓后角浅层的CSPA纤维,可能在新的坐骨神经疼痛动物模型机械刺激痛觉过敏的发生中起着关键作用.     

Comparison of neuropathic pain induced by the application of normal and mechanically compressed nucleus pulposus to lumbar nerve roots in the rat.

We studied whether applying nucleus pulposus tissue, obtained from tail intervertebral discs that had been subjected to chronic mechanical compression, to the lumbar nerve roots produces hyperalgesia, which is thought to be a pain-related behavior in the rat. An Ilizarov-type apparatus was used for immobilization and chronically applied compression of the rat tail for eight weeks. Three weeks after application of extracted nucleus pulposus tissue on the lumbar nerve roots, motor function, sensitivity to noxious mechanical stimuli was measured. Eight weeks after application of the apparatus, the instrumented vertebrae were resected and sections were stained with hematoxylin and eosin to evaluate degeneration of the intervertebral disc. Mechanical hyperalgesia observed in rats treated with the compressed nucleus pulposus tissue was greater and of longer duration than in the rats treated with normal and non-compressed discs. The nucleus pulposus in the instrumented vertebrae showed some histological degeneration. In conclusion, chronic mechanical compression of nucleus pulposus, which resulted in degeneration to some extent, enhanced mechanical hyperalgesia, which was induced by application of nucleus pulposus on the nerve root in the rat. Degenerative intervertebral discs might induce more significant pain than normal intervertebral discs.     

Localization and changes of intraneural inflammatory cytokines and inducible-nitric oxide induced by mechanical compression.

STUDY DESIGN: Investigation of intraneural inflammation induced by mechanical compression. OBJECTIVES: In order to investigate the mechanism of neuropathy, this study used a median nerve compression model in dogs. Immunohistochemistry was used to examine the localization and changes of inflammatory cytokines and nitric oxide (NO). SUMMARY OF BACKGROUND DATA: The manifestation of pain at sites of inflammation has a close relationship with the release of mediators from macrophages such as interleulin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), as well as with NO. However, the mediators involved in inflammation of nerve due to mechanical compression remain almost unknown. METHODS: In this study, the median nerve of dogs was compressed with a clip for three weeks to observe the changes caused by compression. Immunohistochemistry was done by the avidin-biotin-peroxidase complex method to observe the changes of T cells (CD45) and macrophages (Mac-1) after compression. Antibodies against IL-1beta, TNF-alpha, and inducible nitric oxide synthesis (i-NOS) were used to examine the localization and changes of these mediators caused by nerve compression. RESULTS: In control animals, resident T cells were detected, but there were no macrophages. IL-1beta was positive in the Schwann cells and vascular endothelial cells. However, no cells showed TNF-alpha or i-NOS positively. After nerve compression, numerous T cells and macrophages appeared among the demyelinized nerve fibers. The macrophages were positive for IL-1beta, TNF-alpha and i-NOS. CONCLUSION: Inflammatory cytokines and NO may be involved in intraneural inflammatory changes arising from mechanical compression. Such mediators may be of importance in the manifestation of neuropathy.     

Nitric oxide as a mediator of nucleus pulposus-induced effects on spinal nerve roots.

Nerve root dysfunction and sciatic pain in disc herniation are considered to be caused by mechanical compression and related to the presence of nucleus pulposus in the epidural space. Autologous nucleus pulposus has been shown to induce endoneural edema and to decrease nerve-conduction velocity in spinal nerve roots in experimental disc herniation models, and inflammatory mediators have been suggested to be involved in these mechanisms. Nitric oxide, a potent inflammatory mediator, is implicated in vasoregulation, neurotransmission, and neuropathic pain. Nitric oxide synthesis can be induced by different cytokines, e.g., tumor necrosis factor-alpha, which recently was shown to be of pathophysiological importance in experimental disc herniation. The enzyme nitric oxide synthase mediates the production of nitric oxide. Three series of experiments were performed in rat and pig disc herniation models to (a) investigate nitric oxide synthase activity in spinal nerve roots after exposure to autologous nucleus pulposus and (b) evaluate the effects of systemic treatment with aminoguanidine, a nitric oxide synthase inhibitor, on vascular permeability and nerve-conduction velocity. In a disc herniation model in the rat, calcium-independent nitric oxide synthase activity was measured in nerve roots exposed to nucleus pulposus; however, no nitric oxide synthase activity was detected in nerve roots from animals that underwent a sham operation, reflecting increased inducible nitric oxide synthase activity. In nucleus pulposus-exposed spinal nerve roots in the pig, the edema was less severe after systemic aminoguanidine administration than without aminoguanidine treatment. Aminoguanidine treatment also significantly reduced the negative effect of nucleus pulposus on nerve-conduction velocity in spinal nerve roots in the pig. These results demonstrate that nucleus pulposus increases inducible nitric oxide synthase activity in spinal nerve roots and that nitric oxide synthase inhibition reduces nucleus pulposus-induced edema and prevents reduction of nerve-conduction velocity. Furthermore, the results suggest that nitric oxide is involved in the pathophysiological effects of nucleus pulposus in disc herniation.     

Effect of nucleus pulposus on the neural activity of dorsal root ganglion

STUDY DESIGN: This study was designed to investigate, using neurophysiologic techniques in an in vivo rat model, the effect of application of nucleus pulposus to the nerve root on the neural activity of the dorsal root ganglion and the corresponding receptive fields. OBJECTIVES: To assess a further role of the dorsal root ganglion in mechanisms of radicular pain in lumbar disc herniation. SUMMARY OF BACKGROUND DATA: It has been suggested that the epidural application of autologous nucleus pulposus without mechanical compression causes nerve root inflammation and related radicular pain in lumbar disc herniation. Concerning the dorsal root ganglion, its mechanical hypersensitivity and potential for generating ectopic discharges have been reported. However, the effect of autologous nucleus pulposus on the dorsal root ganglion is uncertain. METHODS: In adult Sprague-Dawley rats spontaneous neural activity was recorded from the surgically exposed L5 dorsal root using electrophysiologic techniques, and the mechanosensitivity of L5 dorsal root ganglia and corresponding receptive fields on the hind paw were measured using calibrated nylon filaments. Autologous nucleus pulposus from the tail or fat was implanted at the L5 nerve root. Neural activity was monitored for 6 hours. RESULTS: Spontaneous neural activity in the nucleus pulposus group gradually increased and showed significant differences compared with the fat group from 2.5 to 6 hours after exposure. The mechanosensitivity of the dorsal root ganglia showed significant increases compared with the fat group. CONCLUSIONS: After application of nucleus pulposus to the nerve root, the dorsal root ganglion demonstrated increased excitability and mechanical hypersensitivity. These results suggest that nucleus pulposus causes excitatory changes in the dorsal root ganglion.     

一氧化氮在突出腰椎间盘中的表达及其意义

目的 :研究一氧化氮 (NO)在突出腰椎间盘组织中的含量及组织学定位 ,并对其意义进行探讨。方法 :对 32例腰椎间盘突出患者的突出间盘组织采取两种方法进行研究 :(1) 12例做体外培养 ,用分光光度法测定培养液上清中NO含量 ;(2 ) 2 0例用免疫组化方法对产生NO的细胞类型及组织学定位进行研究。同时对取自 4具新鲜尸体的 12个正常椎间盘采用相同方法做为对照。结果 :突出腰椎间盘组织产生NO的量为 2 0 0 70± 6 5 5 5nmol/g ,正常对照组的NO量为 76 31± 19 49nmol/ g ,两者统计学有显著性差异 (P <0 0 0 1)。免疫组化结果发现 ,2 0例患者椎间盘组织中一氧化氮合成酶表达阳性 16例 ,12个正常椎间盘组织中无表达阳性细胞。结论 :诱导型一氧化氮合成酶主要由突出椎间盘周围的肉芽组织产生 ,阳性细胞主要以成纤维细胞、软骨细胞及淋巴细胞为主。腰椎间盘可自身合成NO ,NO可能在椎间盘退变中起重要作用 ,突出腰椎间盘中的NO主要由突出腰椎间盘周围的肉芽组织产生。     

脑出血患者一氧化氮、一氧化氮合酶的变化及临床意义

目的 探讨一氧化氮(NO)、一氧化氮合酶(NOS)与脑出血的关系。方法 测定76例脑出血患者及66例健康人血浆NO、NOS含量，分析上述指标在出血后3个时期的变化以及与患者颅内血肿量、是否合并蛛网膜下腔出血和临床预后的关系。结果 与对照组相比，脑出血1～3d组NO、NOS含量明显高于4～7d组、14d组和对照组，NO、NOS变化与颅内血肿量和／或合并蛛网膜下腔出血有一定关系。结论 NO、NOS参与了脑出血病理生理过程，其变化对病情的预后有一定的意义。     

一氧化氮在家猪皮肤撕脱伤撕脱皮瓣坏死中的作用

为了探讨一氧氮和一氧化氮合成酶抑制剂－硝基左旋精氨酸甲基酯在撕脱皮瓣坏死中的作用，采用家猪下肢撕脱伤模型，用测量，称重以及微盘，组织化学和原位杂交的方法进行观察。结果：撕脱皮瓣早期ＮＯＳ基因表达增多。